Timothy Manzone

Fractionated radioimmunotherapy with 90Y-clivatuzumab tetraxetan and low-dose gemcitabine is active in advanced pancreatic cancer: A phase 1 trial

It has been demonstrated that the humanized clivatuzumab tetraxetan (hPAM4) antibody targets pancreatic ductal carcinoma selectively. After a trial of radioimmunotherapy that determined the maximum tolerated dose of single‐dose yttrium‐90‐labeled hPAM4 (90Y‐hPAM4) and produced objective responses in patients with advanced pancreatic ductal carcinoma, the authors studied fractionated radioimmunotherapy combined with low‐dose gemcitabine in this disease.

Blood Volume Analysis: A New Technique and New Clinical Interest Reinvigorate a Classic Study

Blood volume studies using the indicator dilution technique and radioactive tracers have been performed in nuclear medicine departments for over 50 y. A nuclear medicine study is the gold standard for blood volume measurement, but the classic dual-isotope blood volume study is time-consuming and can be prone to technical errors. Moreover, a lack of normal values and a rubric for interpretation made volume status measurement of limited interest to most clinicians other than some hematologists. A new semiautomated system for blood volume analysis is now available and provides highly accurate results for blood volume analysis within only 90 min. The availability of rapid, accurate blood volume analysis has brought about a surge of clinical interest in using blood volume data for clinical management. Blood volume analysis, long a low-volume nuclear medicine study all but abandoned in some laboratories, is poised to enter the clinical mainstream. This article will first present the fundamental principles of fluid balance and the clinical means of volume status assessment. We will then review the indicator dilution technique and how it is used in nuclear medicine blood volume studies. We will present an overview of the new semiautomated blood volume analysis technique, showing how the study is done, how it works, what results are provided, and how those results are interpreted. Finally, we will look at some of the emerging areas in which data from blood volume analysis can improve patient care. The reader will gain an understanding of the principles underlying blood volume assessment, know how current nuclear medicine blood volume analysis studies are performed, and appreciate their potential clinical impact.

Imaging of the thyroid in benign and malignant disease.

The thyroid gland was one of the first organs imaged in nuclear medicine, beginning in the 1940s. Thyroid scintigraphy is based on a specific phase or prelude to thyroid hormone synthesis, namely trapping of iodide or iodide analogues (ie, Tc99m pertechnetate), and in the case of radioactive iodine, eventual incorporation into thyroid hormone synthesis within the thyroid follicle. Moreover, thyroid scintigraphy is a reflection of the functional state of the gland, as well as the physiological state of any structure (ie, nodule) within the gland. Scintigraphy, therefore, provides information that anatomical imaging (ie, ultrasound, computed tomography [CT], magnetic resonance imaging) lacks. Thyroid scintigraphy plays an essential role in the management of patients with benign or malignant thyroid disease. In the former, the structure or architecture of the gland is best demonstrated by anatomical or cross-sectional imaging, such as ultrasound, CT, or even magnetic resonance imaging. The role of scintigraphy, however, is to display the functional state of the thyroid gland or that of a clinically palpable nodule within the gland. Such information is most useful in (1) patients with thyrotoxicosis, and (2) those patients whose thyroid nodules would not require tissue sampling if their nodules are hyperfunctioning. In neoplastic thyroid disease, thyroid scintigraphy is often standard of care for postthyroidectomy remnant evaluation and in subsequent thyroid cancer surveillance. Planar radioiodine imaging, in the form of the whole-body scan (WBS) and posttherapy scan (PTS), is a fundamental tool in differentiated thyroid cancer management. Continued controversy remains over the utility of WBS in a variety of patient risk groups and clinical scenarios. Proponents on both sides of the arguments compare WBS with PTS, thyroglobulin, and other imaging modalities with differing results. The paucity of large, randomized, prospective studies results in dependence on consensus expert opinion and retrospective analysis with inherent bias. With a growing trend not to ablate low-risk patients, so that a PTS cannot be performed, some thyroid carcinoma patients may never have radioiodine imaging. In routine clinical practice, however, imaging plays a critical role in patient management both before and after treatment. Moreover, as evidenced by the robust flow of publications concerning WBS and PTS, planar imaging of thyroid carcinoma remains a topic of great interest in this modern age of rapidly advancing cross sectional and hybrid imaging with single-photon emission computed tomography, single-photon emission computed tomography/CT, and positron emission tomography/CT.

Ensuring Safe and Quality Medication Use in Nuclear Medicine: A Collaborative Team Achieves Compliance with Medication Management Standards

As hospital nuclear medicine departments were established in the 1960s and 1970s, each department developed detailed policies and procedures to meet the specialized and specific handling requirements of radiopharmaceuticals. In many health systems, radiopharmaceuticals are still unique as the only drugs not under the control of the health system pharmacy; however, the clear trend—and now an accreditation requirement—is to merge radiopharmaceutical management with the overall health system medication management system. Accomplishing this can be a challenge for both nuclear medicine and pharmacy because each lacks knowledge of the specifics and needs of the other field. In this paper we will first describe medication management standards, what they cover, and how they are enforced. We will describe how we created a nuclear medicine and pharmacy team to achieve compliance, and we will present the results of their work. We will examine several specific issues raised by incorporating radiopharmaceuticals in the medication management process and describe how our team addressed those issues. Finally, we will look at how the medication management process helps ensure ongoing quality and safety to patients through multiple periodic reviews. The reader will gain an understanding of medication management standards and how they apply to nuclear medicine, learn how a nuclear medicine and pharmacy team can effectively merge nuclear medicine and pharmacy processes, and gain the ability to achieve compliance at the readers own institution.

IMPROVING NON-CARDIOLOGIST APPROPRIATE USE OF STRESS MYOCARDIAL PERFUSION IMAGING

Appropriate use (AU) of tests like myocardial perfusion imaging (MPI) is important for delivering efficient, cost-effective care. The American College of Cardiology (ACC) has developed Appropriate Use Criteria (AUC) for MPI. Cardiologists, familiar with AUC, have fewer “rarely appropriate” MPI

Utility of Diagnostic Whole-Body Iodine Scanning in High-Risk Differentiated Thyroid Carcinoma

TO THE EDITOR: de Meer et al. recently published a retrospective study comparing diagnostic whole-body scintigraphy (DxWBS) to stimulated thyroglobulin measurement in patients with high-risk differentiated thyroid cancer (1). The authors concluded that DxWBS offered no additional information compared with recombinant human thyroid-stimulating hormone (rhTSH)–stimulated thyroglobulin levels for this cohort of patients. We would argue that shortcomings in the study design and DxWBS methodology invalidate the authors’ conclusion. The authors defined high-risk patients as those with either T3 or T4 tumors or cervical lymph node metastases (N1) based on American Joint Committee on Cancer (AJCC) TNM version 7 (2). Interestingly, they chose to exclude all patients with distant metastases (M1). However, the authors’ high-risk definition is inconsistent with both American and European guidelines, which include patients with M1 disease in their definitions of high-risk patients (3,4). Moreover, the inclusion and exclusion criteria may have been stated incorrectly: we were surprised to see AJCC TNM stage II patients listed in Table 1 of the article. AJCC TNM stage II is defined as either M1 disease in patients less than 45 y old or T2N0M0 for patients more than 45 y old. Since both of these subsets of patients were purportedly excluded, stage II patients should not have appeared in the group analyzed. This inconsistency warrants explanation or correction. The authors did not take into account age when risk stratifying their patients since European treatment guidelines are independent of age. However, age is considered the most important prognostic variable for mortality by the American National Comprehensive Cancer Network guidelines, with higher mortality in patients over 40 y old (5). For papillary and follicular thyroid carcinoma, AJCC TNM staging defines all patients less than 45 y old as either stage I or stage II, including patients with distant metastases. In a study validating AJCC TNM classification and group staging for patients with papillary thyroid carcinoma, age was an independent predictor of both disease-free survival and cause-specific survival (6). Not using the age for risk stratification in such a study renders the results irrelevant to nuclear medicine practices in the United States. In their study, the authors performed DxWBS with thyroid hormone withdrawal (THW) between January 1998 and December 2004 and then switched to rhTSH exclusively from January 2005 to January 2009. However, the original phase III clinical trial comparing rhTSH and THW preparation for DxWBS concluded that rhTSH DxWBS was less sensitive than DxWBS using THW (7). In this phase III trial, rhTSH DxWBS was inferior to THW DxWBS in 18 (29%) of 62 patients and failed to detect metastatic disease in 8 (13%) of 62 patients with positive scans. A second phase III clinical trial, again comparing rhTSH and THW preparation for DxWBS, also showed that rhTSH DxWBS was inferior to THW DxWBS in 8 (16%) of 49 of patients with metastatic disease (8). Although this difference was not statistically significant (p 5 0.109), the trend favored THW DxWBS. As a result, we believe that rhTSH DxWBS should be reserved for low-risk patients only, an approach supported by the package insert for rhTSH itself. Moreover, the authors waited 7 d after 131I administration to perform the DxWBS (European guidelines recommend between 2 and 5 d) and used twice the recommended 131I activity; these factors make their technique impossible to compare with standard practices. Relying on rhTSH-stimulated thyroglobulin for detection of recurrence has its perils. Comparing 131I rhTSH-stimulated DxWBS to thyroglobulin during routine follow-up evaluations, Robbins et al. found metastatic thyroid carcinoma on DxWBS in 13.7% of patients of all risk categories with stimulated thyroglobulin of 2 mg/L or less (9). The authors of the present paper mentioned the conclusion of Robbins et al. but left a huge gap in the discussion by offering no explanation as to why their own results and conclusions were so different from those of Robbins et al. Only the DxWBS can show iodine avidity and guide the decision on whether to treat the patients with 131I or with surgery. In the United States, DxWBS remains the gatekeeper to more advanced imaging with 18F-FDG PET, as most insurance companies require both elevated thyroglobulin levels and negative DxWBS findings to reimburse PET. Omitting the DxWBS would make 18F-FDG PET unavailable to patients in the United States. The deMeer et al. study addressed a very narrow segment of high-risk thyroid carcinoma patients, did not follow accepted risk stratification guidelines, and does not help many of us who use age in this stratification. The striking deficiencies of this work are the application of rhTSH-stimulated DxWBS to a high-risk group in which it is considered to be inferior to THW DxWBS, the use of nonstandard imaging techniques, and the notion that disease location and iodine avidity are irrelevant to patient management. The readers are encouraged to keep these issues in mind as they evaluate high-risk thyroid cancer patients.